Joenja: which tox species, and why?

“The Applicant has conducted subchronic and chronic toxicology studies with leniolisib in both rats and cynomolgus monkeys.”

“Characterization and structural elucidation of metabolites in plasma, urine or bile from nonclinical species have demonstrated the similarities in the metabolic profiles between these species and humans. It is noted that no major human metabolites were identified in completed clinical studies.”

“Rats (20/sex/group) were exposed to 0, 15, 40, and 120 mg/kg/day of leniolisib for 26 weeks via oral gavage with additional animals included in the control and HD groups for a 4-week recovery period.”

“The Applicant has conducted subchronic and chronic toxicology studies with leniolisib in both rats and cynomolgus monkeys.”

“In animal reproduction studies, oral administration of leniolisib to pregnant rats and rabbits during the period of organogenesis at exposures approximately 2-6 times the MRHD on an AUC basis, produced embryofetal toxicity including malformations.”

“The 6-month transgenic (Tg-RasH2) mouse carcinogenicity study and 2-year carcinogenicity study with rats are ongoing under Special Protocol Assessments with ECAC concurrence.”

“The Applicant has conducted subchronic and chronic toxicology studies with leniolisib in both rats and cynomolgus monkeys.”